Deep Learning-Based Techniques in Glioma Brain Tumor Segmentation Using Multi-Parametric MRI: A Review on Clinical Applications and Future Outlooks.

This comprehensive review explores the role of deep learning (DL) in glioma segmentation using multiparametric magnetic resonance imaging (MRI) data. The study surveys advanced techniques such as multiparametric MRI for capturing the complex nature of gliomas. It delves into the integration of DL with MRI, focusing on convolutional neural networks (CNNs) and their remarkable capabilities in tumor segmentation. Clinical applications of DL-based segmentation are highlighted, including treatment planning, monitoring treatment response, and distinguishing between tumor progression and pseudo-progression. Furthermore, the review examines the evolution of DL-based segmentation studies, from early CNN models to recent advancements such as attention mechanisms and transformer models. Challenges in data quality, gradient vanishing, and model interpretability are discussed. The review concludes with insights into future research directions, emphasizing the importance of addressing tumor heterogeneity, integrating genomic data, and ensuring responsible deployment of DL-driven healthcare technologies. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2.

Emerging drugs for the treatment of irritability associated with autism spectrum disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is an early-onset disorder with a prevalence of 1% among children and reported disability-adjusted life years of 4.31 million. Irritability is a challenging behavior associated with ASD, for which medication development has lagged. More specifically, pharmacotherapy effectiveness may be limited against high adverse effects (considering side effect profiles and patient medication sensitivity); thus, the possible benefits of pharmacological interventions must be balanced against potential adverse events in each patient. AREAS COVERED: After reviewing the neuropathophysiology of ASD-associated irritability, the benefits and tolerability of emerging medications in its treatment based on randomized controlled trials were detailed in light of mechanisms and targets of action. EXPERT OPINION: Succeeding risperidone and aripiprazole, monotherapy with memantine may be beneficial. In addition, N-acetylcysteine, galantamine, sulforaphane, celecoxib, palmitoylethanolamide, pentoxifylline, simvastatin, minocycline, amantadine, pregnenolone, prednisolone, riluzole, propentofylline, pioglitazone, and topiramate, all adjunct to risperidone, and clonidine and methylphenidate outperformed placebo. These effects were through glutamatergic, γ-aminobutyric acidergic, inflammatory, oxidative, cholinergic, dopaminergic, and serotonergic systems. All medications were reported to be safe and tolerable. Considering sample size, follow-up, and effect size, further studies are necessary. Along with drug development, repositioning and combining existing drugs supported by the mechanism of action is recommended.

Crocin (bioactive compound of Crocus sativus L.) potently restores REM sleep deprivation-induced manic- and obsessive-compulsive-like behaviors in female rats.

Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors including hyperlocomotion. On the other hand, crocin (one of the main compounds of Crocus sativus L. or Saffron) may be beneficial in the improvement of mental and cognitive dysfunctions. Also, crocin can restore the deleterious effects of SD on mental and cognitive processes. In this study, we investigated the effect of REM SD on female rats' behaviors including depression- and anxiety-like behaviors, locomotion, pain perception, and obsessive-compulsive-like behavior, and also, the potential effect of crocin on REM SD effects. We used female rats because evidence on the role of REM SD in modulating psychological and behavioral functions of female (but not male) rats is limited. REM SD was induced for 14 days (6h/day), and crocin (25, 50, and 75 mg/kg) was injected intraperitoneally. Open field test, forced swim test, hot plate test, and marble burying test were used to assess rats' behaviors. The results showed REM SD-induced manic-like behavior (hyperlocomotion). Also, REM SD rats showed decreased anxiety- and depression-like behavior, pain subthreshold (the duration it takes for the rat to feel pain), and showed obsessive compulsive-like behavior. However, crocin at all doses partially or fully reversed REM SD-induced behavioral changes. In conclusion, our results suggested the possible comorbidity of OCD and REM SD-induced manic-like behavior in female rats or the potential role of REM SD in the etiology of OCD, although more studies are needed. In contrast, crocin can be a possible therapeutic choice for decreasing manic-like behaviors.

The effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy in type II diabetes mellitus patients: A clinical trial.

INTRODUCTION: Diabetic retinopathy (DR) is one of the most threatening complications of diabetes and a leading cause of visual loss in working-age population. Although exercise is beneficial in diabetes, previous studies have showed contradictory and inconclusive results on how it effects DR. In this study, we aimed to investigate the effect of moderate-intensity aerobic exercise on non-proliferative diabetic retinopathy. MATERIALS & METHODS: In this before-after clinical trial, 40 patients with diabetic retinopathy were enrolled by convenient sampling method in Shahid Labbafinejad Hospital in Tehran during 2021-2022. Before the intervention, central macular thickness (CMT, microns) measured by optical coherence tomography (OCT) and fasting blood sugar (FBS, mg/dl) were obtained. Then, patients took part in a 12-week moderate-intensity aerobic exercise (3 sessions per week, each session 45 min). Data were analyzed using SPSS version 26.0. RESULTS: Out of 40 examined patients, 21 (52.5 %) were male and 19 (47.5 %) were female. The mean age of the patients was 50.8 years. The mean rank of FBS (mg/dl) significantly decreased from 21.12 before the exercise to 8.75 after the exercise (p < 0.001). Also, the mean rank of CMT (microns) showed a significant decrease from 21.11 before the intervention to 16.20 after the exercise (p < 0.001). There was a significant positive correlation between patients' age and FBS (mg/dl) before (rho = 0.457, p = 0.003) and after (rho = 0.365, p = 0.021) the intervention. Also, a significant positive correlation was found between patients' age and CMT (microns) before (rho = 0.525, p = 0.001) and after (rho = 0.461, p = 0.003) moderate exercise. CONCLUSION: Moderate-intensity aerobic exercise leads to lower FBS (mg/dl) and CMT (microns) in patients with diabetic retinopathy, so it may be beneficial for diabetic patients to avoid sedentary lifestyle.

Preparatory activity of anterior insula predicts conflict errors: integrating convolutional neural networks and neural mass models.

Preparatory brain activity is a cornerstone of proactive cognitive control, a top-down process optimizing attention, perception, and inhibition, fostering cognitive flexibility and adaptive attention control in the human brain. In this study, we proposed a neuroimaging-informed convolutional neural network model to predict cognitive control performance from the baseline pre-stimulus preparatory electrophysiological activity of core cognitive control regions. Particularly, combined with perturbation-based occlusion sensitivity analysis, we pinpointed regions with the most predictive preparatory activity for proactive cognitive control. We found that preparatory arrhythmic broadband neural dynamics in the right anterior insula, right precentral gyrus, and the right opercular part of inferior frontal gyrus (posterior ventrolateral prefrontal cortex), are highly predictive of prospective cognitive control performance.  The pre-stimulus preparatory activity in these regions corresponds to readiness for conflict detection, inhibitory control, and overall elaborate attentional processing. We integrated the convolutional neural network with biologically inspired Jansen-Rit neural mass model to investigate neurostimulation effects on cognitive control. High-frequency stimulation (130 Hz) of the left anterior insula provides significant cognitive enhancement, especially in reducing conflict errors, despite the right anterior insula's higher predictive value for prospective cognitive control performance. Thus, effective neurostimulation targets may differ from regions showing biomarker activity. Finally, we validated our theoretical finding by evaluating intrinsic neuromodulation through neurofeedback-guided volitional control in an independent dataset. We found that left anterior insula was intrinsically modulated in real-time by volitional control of emotional valence, but not arousal. Our findings further highlight central role of anterior insula in orchestrating proactive cognitive control processes, positioning it at the top of hierarchy for cognitive control.

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

BACKGROUND: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. METHODS: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. RESULTS: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. CONCLUSIONS: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated.

Emerging pharmacotherapy for the treatment of cannabis use disorder.

INTRODUCTION: About one-fifth of cannabis users, the most commonly used illicit substance, have cannabis use disorder (CUD). Psychiatric disorders and suicide are more common in these patients, and the disability-adjusted life years were reported to be 0.69 million. Pharmacotherapy for CUD is an unmet public health need, as current evidence-based therapies have limited efficacy. AREAS COVERED: After explaining the pathophysiology of CUD, the effects of emerging pharmacological interventions in its treatment obtained from randomized controlled trials were reviewed in light of mechanisms of action. Superiority over control of cannabidiol, gabapentin, galantamine, nabilone plus zolpidem, nabiximols, naltrexone, PF-04457845, quetiapine, varenicline, and topiramate were observed through the cannabinoid, glutamatergic, γ-aminobutyric acidergic, serotonergic, noradrenergic, dopaminergic, opioidergic, and cholinergic systems. All medications were reported to be safe and tolerable. EXPERT OPINION: Adding pharmacotherapy to psychotherapy is the optimal treatment for CUD on a case-by-case basis. Drug development to add to psychotherapy is the main path, but time and cost suggest repurposing and repositioning existing drugs. Considering sample size, follow-up, and effect size, further studies using objective tools are necessary. The future of CUD treatment is promising.

Machine learning and artificial intelligence within pediatric autoimmune diseases: applications, challenges, future perspective.

INTRODUCTION: Autoimmune disorders affect 4.5% to 9.4% of children, significantly reducing their quality of life. The diagnosis and prognosis of autoimmune diseases are uncertain because of the variety of onset and development. Machine learning can identify clinically relevant patterns from vast amounts of data. Hence, its introduction has been beneficial in the diagnosis and management of patients. AREAS COVERED: This narrative review was conducted through searching various electronic databases, including PubMed, Scopus, and Web of Science. This study thoroughly explores the current knowledge and identifies the remaining gaps in the applications of machine learning specifically in the context of pediatric autoimmune and related diseases. EXPERT OPINION: Machine learning algorithms have the potential to completely change how pediatric autoimmune disorders are identified, treated, and managed. Machine learning can assist physicians in making more precise and fast judgments, identifying new biomarkers and therapeutic targets, and personalizing treatment strategies for each patient by utilizing massive datasets and powerful analytics.

Shining a Light on Selenium: a Meta-analysis of Supplementation in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disease of the central nervous system. Selenium is a trace element with significant antioxidant activity. This study aimed to seek evidence concerning selenium supplementation in MS. A systematic search was performed on PubMed, Web of Science, Scopus, and Embase databases to identify the studies assessing the consumption rate, efficacy, and safety of selenium and selenium-containing supplementations in MS patients. The meta-analysis was performed using the Comprehensive Meta-Analysis and the risk of bias was evaluated using the Joanna Briggs Institute's critical appraisal tools. A total of 9 studies were included, which consisted of six studies regarding the rate of selenium supplement consumption in MS patients, with a total sample size of 2381 patients. Based on the quantitative synthesis, 14.3% (95% CI, 12.8-16.0%; I2, 3.58%) of MS patients had current selenium supplements usage, and 11.3% (95% CI, 7.6-16.6%; I2, 81.40%) of patients had used selenium supplements previously. Although there is no evidence regarding supplementation with selenium alone, three RCT studies reported the safety of selenium-containing supplementation use in MS with improved inflammation and oxidative stress conditions. The findings of this study show that over 10% of patients with MS used selenium supplements, with no clinical significance supporting the benefits. There is a lack of evidence regarding the safety and efficacy of selenium supplements in MS patients. Due to the limited number of included studies and the lack of comprehensive and specific studies regarding selenium supplements in MS, the results must be interpreted with caution, and future clinical trials are required.

Sex-controlled differences in sertraline and citalopram efficacies in major depressive disorder: a randomized, double-blind trial.

To investigate the response to antidepressants while controlling for sex, which has been controversial, 92 outpatient males and females with major depressive disorder were assigned to sertraline (100 mg/day) or citalopram (40 mg/day) in two strata and were assessed using Hamilton depression rating scale (HDRS) scores and brain-derived neurotrophic factor (BDNF), interleukin (IL)-6 and cortisol serum levels in this 8-week, randomized, parallel-group, double-blind clinical trial. Data of 40 sertraline and 40 citalopram recipients with equal representation of males and females assigned to each medication were analyzed, while their baseline characteristics were not statistically different (P > 0.05). There were no significant differences between sertraline and citalopram recipients in outcome changes (P > 0.05), all of which indicated improvement, but a significant time-treatment-sex interaction effect in BDNF levels was observed (P = 0.035). Regarding this, subgroup analyses illustrated a significantly greater increase in male BDNF levels following sertraline treatment (P = 0.020) with a moderate to large effect size (Cohen's d = 0.76 and ). Significant associations were observed between percentage changes in IL-6 levels and BDNF levels in sertraline recipients (P = 0.033) and HDRS scores in citalopram recipients (P < 0.001). Sex was an effect modifier in BDNF alterations following sertraline and citalopram administration. Further large-scale, high-quality, long-term studies are recommended.

Serum lipids and cognitive outcomes in multiple sclerosis; a systematic review and meta-analysis.

BACKGROUND: Cognitive impairment is highly prevalent in multiple sclerosis (MS) with poorly understood underlying mechanisms. Lipids are considered to be associated with MS progression through the inflammatory and oxidative stress pathways, brain atrophy, cellular signaling, and tissue physiology. In addition, serum lipids are proposed as a modifiable factor affecting the neuropsychiatric condition; therefore, this study aims to assess the association between serum lipid levels and cognitive outcomes in MS. METHODS: This study was carried out following the PRISMA 2020 statement. A systematic search was conducted in PubMed, Scopus, Web of Science, and Embase in March 2023, and the Joanna Briggs Institute (JBI)'s critical appraisal tools were utilized for risk of bias (RoB) assessments in the included studies. The quantitative synthesis was performed with the comprehensive meta-analysis (CMA3) software. RESULTS: Out of 508 screened records, 7 studies were eventually found to meet our inclusion criteria. In two studies, the course of MS in the sample of the study was only Relapsing-Remitting MS (RRMS), whereas the other five studies' sample was a combination of different phenotypes. Studies utilized different scales such as Minimal Assessment of Cognitive Function in MS (MACFIMS), Brief International Cognitive Assessment for MS (BICAMS), Montreal Cognitive Assessment (MoCA), Brief Repeatable Battery of Neuropsychological Tests (BRB-N) for cognitive evaluations. Dealing with possible confounders such as age, disease duration and level of disability was the most common possible source of bias in the included studies. One study revealed an inverse relationship between serum levels of apolipoproteins (including ApoA-I, ApoB, and ApoB/ApoA-I) and Symbol Digit Modalities Test (SDMT) scores. Also, a correlation between 24S-hydroxycholesterol (24OHC) serum concentrations and SDMT score was reported in one study. The association between serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) and different aspects of cognitive function was reported in the studies; however, serum levels of high-density lipoprotein cholesterol (HDL) were not found to be associated. The quantitative synthesis revealed a significant correlation between TC and the MoCA scores (r =-0.238; 95 %CI: -0.366 to -0.100; p-value = 0.001); however, the correlation between TG levels and MoCA were not statistically significant (r:-0.070; 95 %CI: -0.209 to 0.072; p-value: 0.334). In addition, the mata-analyses were not associated with significant findings regarding the correlation between lipid profiles (including HDL, LDL, TG, and TC) and other cognitive assessment scales including SDMT, Brief Visuospatial Memory Test (BVMT), and California Verbal Learning Test (CVLT) (p-values>0.05). DISCUSSION: Available evidence suggested a link between TC and LDL with cognitive outcomes of MS patients which was not evident in our quantitative synthesis. The limited number of studies, high RoB, different cognitive assessment scales and reporting methods, and the cross-sectional design of the included studies, were the main limitations that alleviate the clinical significance of the findings of this study and suggested further investigations on this topic. FUNDING AND REGISTRATION: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 71,909). This study is registered in the international prospective register of systematic reviews (PROSPERO ID: CRD42023441625).

Recent advances in fluorescence nanoparticles "quantum dots" as gene delivery system: A review.

Biomaterial scientists have recently focused their attention on evaluating various aspects of delivering genetic materials into cells to induce a cellular response. The process involves complexing negatively charged plasmids, followed by delivering the resulting package into cells, a process facilitated by lipids, peptides, viruses, synthetically modified cationic polymers, and specific inorganic nanomaterials. In the context of gene delivery for specific imaging in biological and biomedical applications, fluorescence nanocrystals or quantum dots (QDs) present promising candidates as engineered nanoparticles (NPs). This literature review study aims to investigate the potential of QDs as a novel tool for gene delivery to retinal cells. The proficiency of QDs in this context arises from their unique physicochemical characteristics, including optical electronic and catalytic properties, which render them viable options for biosensing imaging, drug delivery, and gene delivery applications. In the field of gene delivery to the retinal cells, factors such as photoluminescence, quantum yield, biocompatibility, size, and shape play crucial roles in the utilization of QDs. In this paper, we discuss the most appropriate credentials and briefly outline the findings, supported by relevant illustrative samples, to explore the delivery of genetic material utilizing QDs.

A systematic review of clinical efficacy and safety of cell-based therapies in Alzheimer's disease.

There is presently no disease-modifying therapy for Alzheimer's Disease (AD), which is the most prevalent cause of dementia. Objective: This study aspires to estimate the efficacy and safety of cell-based treatments in AD. Methods: Observing the Joanna Briggs Institute (JBI) methods and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search was accomplished in PubMed, Medical Literature Analysis and Retrieval System Online (Medline, via Ovid), Embase; Cochrane, and Cumulative Index of Nursing and Allied Health Literature - CINAHL (via EBSCO) databases up to June 2023. The relevant clinical studies in which cell-based therapies were utilized to manage AD were included. The risk of bias was evaluated using the JBI checklists, based on the study designs. Results: Out of 1,014 screened records, a total of five studies with 70 individuals (including 59 patients receiving stem cells and 11 placebo controls) were included. In all these studies, despite the discrepancy in the origin of stem cells, cell density, and transplant site, safety goals were obtained. The intracerebroventricular injection of adipose-derived stromal vascular fraction (ADSVF) and umbilical cord-derived mesenchymal stem cells (UC-MSCs), the intravenous injection of Lomecel-B, and the bilateral hippocampi and right precuneus injection of UC-MSCs are not linked to any significant safety concerns, according to the five included studies. Studies also revealed improvements in biomarkers and clinical outcomes as a secondary outcome. Three studies had no control groups and there are concerns regarding the similarity of the groups in others. Also, there is considerable risk of bias regarding the outcome assessment scales. Conclusion: Cell-based therapies are well tolerated by AD patients, which emphasizes the need for further, carefully planned randomized studies to reach evidence-based clinical recommendations in this respect.

Atualmente, não há terapia modificadora da doença para a doença de Alzheimer (DA), que é a causa mais prevalente de demência. Objetivo: Este estudo teve como objetivo estimar a eficácia e segurança dos tratamentos baseados em células na DA. Métodos: Observando os métodos do JBI e a declaração PRISMA, uma busca sistemática foi realizada nas bases de dados PubMed, Medical Literature Analysis and Retrieval System Online ­ Medline (via Ovid), Embase, Cochrane e CINAHL (via EBSCO) até junho de 2023. Foram incluídos os estudos clínicos relevantes nos quais terapias baseadas em células foram utilizadas para gerenciar a DA. O risco de viés foi avaliado utilizando os checklists do JBI, com base nos desenhos dos estudos. Resultados: Dos 1.014 registros examinados, foi incluído um total de cinco estudos com 70 indivíduos (incluindo 59 pacientes que receberam células-tronco e 11 controles de placebo). Em todos esses estudos, apesar da discrepância na origem das células-tronco, densidade celular e local de transplante, os objetivos de segurança foram alcançados. A injeção intracerebroventricular de ADSVF e UC-MSCs, a injeção intravenosa de Lomecel-B e a injeção bilateral dos hipocampos e precuneus direito de UC-MSCs não estão relacionadas a quaisquer preocupações significativas de segurança, de acordo com os cinco estudos incluídos. Os estudos também revelaram melhorias nos biomarcadores e resultados clínicos como um desfecho secundário. Três estudos não tinham grupos de controle e há preocupações quanto à semelhança dos grupos em outros. Além disso, há um risco considerável de viés em relação às escalas de avaliação de desfechos. Conclusão: As terapias baseadas em células são bem toleradas por pacientes com DA, o que enfatiza a necessidade de mais estudos randomizados cuidadosamente planejados para alcançar recomendações clínicas baseadas em evidências.

Unveiling the lead exposure attributed burden in Iran from 1990 to 2019 through the lens of the Global Burden of Disease study 2019.

This study aimed to investigate the estimated burden attributed to lead exposure (LE), at the national and subnational levels from 1990 to 2019 in Iran. The burden attributed to LE was determined through the estimation of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs) and years lived with disability (YLDs) using the comparative risk assessment method of Global Burden of Disease (GBD) study presenting as age-standardized per 100,000 person year (PY) with 95% uncertainty intervals (95% UI). Furthermore, the burden of each disease were recorded independently. Eventually, the age-standardized YLLs, DALYs, deaths and YLDs rates attributed to LE demonstrated a decrease of 50.7%, 48.9%, 38.0%, and 36.4%, respectively, from 1990 to 2019. The most important causes of LE burden are divided into two acute and chronic categories: acute, mainly causes mental disorders (DALYs rate of 36.0 in 2019), and chronic, results in cardiovascular diseases (CVDs) (DALYs rate of 391.8) and chronic kidney diseases (CKDs) (DALYs rate of 26.6), with CVDs bearing the most significant burden. At the sub-national level, a decrease in burden was evident in most provinces; moreover, low and low-middle SDI provinces born the highest burden. The burden increased mainly by ageing and was higher in males than females. It was concluded that although the overall decrease in the burden; still it is high, especially in low and low-middle SDI provinces, in advanced ages and in males. Among IDID, CKDs and CVDs that are the most important causes of LE-attributed burden in Iran; CVDs bear the highest burden.

Vertical transmission and maternal passive immunity post-SARS-CoV-2.

Since 2020, the highly contagious nature and various transmission routes of SARS-CoV-2 have rendered the pandemic interminable. Vertical transmission (VT) through the placenta and breast milk, which is frequent for certain virus types, is thought to exist for SARS-CoV-2 and is hypothesized by many researchers. Conversely, antibodies are produced to counteract the effect of viruses. Since newborns' immunologic system cannot produce proper antibodies, maternal antibodies are usually transferred from mother to infant/fetus to meet the need. This theory leads to the hypothesis of transmission of antibodies through the placenta and breast milk following SARS-CoV-2 infection or vaccination. This paper further discusses these hypotheses, considering consequences of fetus/infant harm versus benefit.

Unusual presentation of transthyretin (ATTR) cardiac amyloidosis: A case report of pruritus as a possible initial symptom and challenging diagnosis.

Key Clinical Message: This case emphasizes the significance of cardiac amyloidosis as a potential diagnosis in individuals manifesting with lesion-free pruritus and normal liver tests. Abstract: Amyloidosis is a complex disorder in which misfolded proteins accumulate in various organs of the body. Cardiac amyloidosis (CA) can lead to heart failure, cardiac arrhythmia, sudden cardiac death, and deposition of proteins in coronary arteries. Diagnosing CA can be difficult, as the cardiac manifestations of amyloidosis can be similar to more prevalent etiologies. In addition, the accumulation of proteins in soft tissues, including the skin, can cause pruritus. In this paper, we present a 70-year-old man with generalized pruritus and no skin lesions, later diagnosed as CA after detecting ascites fluid. This case underscores the importance of considering amyloidosis in patients presenting with nonspecific symptoms, particularly those affecting the skin, and highlights the need for increased awareness of this disease among clinicians.

Early occurrence of acute myelomonocytic leukemia (M4/M5) after liver transplantation: a case report.

INTRODUCTION: Acute myeloid leukemia is a rare event in post-liver-transplantation recipients. In the present report, we described a case of extramedullary acute myeloid leukemia, M4/M5 subtype, following orthotopic liver transplant. CASE PRESENTATION: The patient was a 50-year-old Iranian woman who underwent orthotopic liver transplant due to hepatitis B-related cirrhosis (Child C, MELD (model for end-stage liver disease score) = 22). Orthotopic liver transplant was performed using the piggy back technique in January 2022. Induction immunosuppressive therapy was 1 gm methylprednisolone for 3 days followed by a triple maintenance immunosuppressive regimen including mycophenolate mofetil, prednisolone, and tacrolimus. About 5 months after orthotopic liver transplant in June 2022, the patient presented with leukocytosis, with white blood cell count of 99.4 × 103/µl, and physical examination revealed only cervical lymphadenopathy. Biopsy of cervical lymph nodes showed a myeloid tumor. She was immediately hospitalized. Eight hours after hospitalization, the patient gradually developed lethargy and decreased O2 saturation to approximately 89%. Flow cytometry demonstrated the markers of a myelomonocytic acute myeloid leukemia (M4/M5). Cytoreduction was immediately started by intensive leukopheresis followed by induction therapy. Because of a septic complication during the induction therapy, further chemotherapy was discontinued and broad-spectrum antibiotics and antifungal treatments started. Unfortunately, our patient died of severe septic shock 42 days after hospitalization. CONCLUSION: Acute myeloid leukemia is a rare phenomenon after liver transplantation, and it can follow a rapidly fatal clinical course.

COVID-19 in Patients with Rheumatic Disease Using Immunomodulatory Drugs: Imaging Findings and Predictors of Hospitalization.

Introduction: SARS-CoV-2 causes more severe symptoms in most chronic diseases, and rheumatic disease is no exception. This study aims to investigate whether there is an association between the use of immunomodulatory medications, including conventional disease-modifying agents (csDMARDs), glucocorticoids, and biologic DMARDs, and outcomes such as hospitalization and lung involvement in patients with rheumatic disease with COVID-19. Methods: We performed a cross-sectional study on 177 COVID-19 cases with rheumatologic diseases using immunomodulatory drugs as their regular treatment. All patients were evaluated regarding their initial chest computed tomography (CT) scan, COVID-19 symptoms, and comorbidities. We ran predictive models to find variables associated with chest CT-scan involvement and hospitalization status. Results: CT findings showed lung involvement in 87 patients with chest CT-scan severity score (C-ss) of less than 8 in 59 (33%) and more than 8 in 28 (16%) of our patients. Of all patients, 76 (43%) were hospitalized. Hospitalized patients were significantly older and had more comorbidities (P = 0.02). On multivariate analysis, older age [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.31-3.08] and comorbidity (OR 2.75, 95% CI 1.06-3.66) were significantly associated with higher odds of hospitalization (P = 0.03). On multivariate analysis, older age (OR 1.15, 95% CI 0.94-2.01), pulmonary diseases (OR 2.05, 95% CI 1.18-3.32), and treatment with csDMARDs (OR 1.88, 95% CI 0.37-1.93) were associated with higher C-ss (P = 0.039). Conclusions: This study found that advanced age and comorbidities, similar to the general population, are risk factors for hospitalization in patients with COVID-19 with rheumatic disorders. Administration of csDMARDs, older age, and pulmonary disorders were linked to increased risk of COVID-19 pneumonia in these individuals.

Neuroimaging Correlates of Treatment Response to Transcranial Magnetic Stimulation in Bipolar Depression: A Systematic Review.

Transcranial magnetic stimulation (TMS) has become a promising strategy for bipolar disorder (BD). This study reviews neuroimaging findings, indicating functional, structural, and metabolic brain changes associated with TMS in BD. Web of Science, Embase, Medline, and Google Scholar were searched without any restrictions for studies investigating neuroimaging biomarkers, through structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), functional MRI (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and single photon emission computed tomography (SPECT), in association with response to TMS in patients with BD. Eleven studies were included (fMRI = 4, MRI = 1, PET = 3, SPECT = 2, and MRS = 1). Important fMRI predictors of response to repetitive TMS (rTMS) included higher connectivity of emotion regulation and executive control regions. Prominent MRI predictors included lower ventromedial prefrontal cortex connectivity and lower superior frontal and caudal middle frontal volumes. SPECT studies found hypoconnectivity of the uncus/parahippocampal cortex and right thalamus in non-responders. The post-rTMS changes using fMRI mostly showed increased connectivity among the areas neighboring the coil. Increased blood perfusion was reported post-rTMS in PET and SPECT studies. Treatment response comparison between unipolar depression and BD revealed almost equal responses. Neuroimaging evidence suggests various correlates of response to rTMS in BD, which needs to be further replicated in future studies.

Paraneoplastic acute eosinophilic pneumonia due to carotid angiosarcoma: A rare case.

Key Clinical Message: This case report emphasizes that we should analyze a patient's signs and symptoms as a whole rather than relying exclusively on a common pattern to diagnose the condition and indicates that thorough histological investigation and sample collection are needed to accurately diagnose this malignancy. Abstract: Angiosarcoma is a rare, fatal, and poorly understood malignant tumor of vascular endothelial cells which is a challenging disease to diagnose in the clinical settings and requires early diagnosis to achieve a favorable prognosis. Paraneoplastic syndromes associated with angiosarcoma can include hypercoagulability, thrombocytopenia, anemia, fever, weight loss, and night sweats. In some cases, the paraneoplastic syndrome can be the first sign of the underlying malignancy. Here, we present a 47-year-old individual with angiosarcoma over the right scapula accompanied by hemoptysis and other pulmonary complaints whom at first was thought to be metastatic polmunary involvement. However, the patient's dramatic response to corticosteroids, in addition to further imaging and paraclinical studies, led us to an acute eosinophilic pneumonia (AEP) diagnosis which is an eosinophilic infiltrations of alveolar spaces. The patient received chemotherapy for angiosarcoma and radiation, since the brachial nerve network was disrupted, leaving the tumor unresectable. After 3 years of continuous follow-up, the patient is now completely cured.